ArticleProceedings of the National Academy of Sciences of the United States of America2012
Tumor suppressor function of Liver kinase B1 (Lkb1) is linked to regulation of epithelial integrity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Pooled it
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- Towards Precision Oncology: How Advances in Cancer Genomics, Immunobiology and Artificial Intelligence Will Change Molecular Diagnostics.Biomedicines · 2026Review
- Article
- Hepsin promotes breast tumor growth signaling via the TGFβ-EGFR axis.Molecular oncology · 2024Article
- Bone morphogenetic protein 2- and estradiol-17β-induced changes in ovarian transcriptome during primordial follicle formation†.Biology of reproduction · 2022Article
- Metabolic determination of cell fate through selective inheritance of mitochondria.Nature cell biology · 2022Article
- Compressive stress-mediated p38 activation required for ERα + phenotype in breast cancer.Nature communications · 2021Article
- Hepsin regulates TGFβ signaling via fibronectin proteolysis.EMBO reports · 2021Article
- Article
- An investigation of the relationship between TMPRSS6 gene expression, genetic variants and clinical findings in breast cancer.Molecular biology reports · 2020Article
- Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.Cell death & disease · 2019Article
- Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy.Nature communications · 2019Article
- Anakoinosis: Correcting Aberrant Homeostasis of Cancer Tissue-Going Beyond Apoptosis Induction.Frontiers in oncology · 2019Review
- Intestinal Epithelial Cell-Derived LKB1 Suppresses Colitogenic Microbiota.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Prognostic significance of LKB1 promoter methylation in cutaneous malignant melanoma.Oncology letters · 2017Article
- Post-translational regulation contributes to the loss of LKB1 expression through SIRT1 deacetylase in osteosarcomas.British journal of cancer · 2017Article
- The role of type II transmembrane serine protease-mediated signaling in cancer.The FEBS journal · 2017Review
- MYC and AMPK-Save Energy or Die!Frontiers in cell and developmental biology · 2017Review
- Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Although loss of epithelial integrity is a hallmark of advanced cancer, it remains poorly understood whether genetic alterations corrupting this integrity causally facilitate tumorigenesis. We show that conditional deletion of tumor suppressor gene Lkb1 (Par-4) in the mammary gland compromises epithelial integrity manifested by mislocalization of cell polarity markers, lateralization of tight junctions, deterioration of desmosomes and basement membrane (BM), and hyperbranching of the mammary ductal tree. We identify the desmosomal BM remodelling serine protease Hepsin as a key factor mediating Lkb1 loss-induced structural alterations in mammary epithelium and BM fragmentation. Although loss of Lkb1 alone does not promote mammary tumorigenesis, combination of Lkb1 deficiency with oncogenic c-Myc leads to dramatic acceleration in tumor formation. The results coupling Lkb1 loss-mediated epithelial integrity defects to mislocalization of serine protease Hepsin and to oncogenic synergy with c-Myc imply that Lkb1 loss facilitates oncogenic proliferation by releasing epithelial cells from structural BM boundaries.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.